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Background Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data. Methods Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models. Results Among 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10–2.58)] and subtypes ALL [1.49 (0.87–2.56)] and AML [2.70 ([0.93–7.86)], but not with any cancer [1.13 (0.85–1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06–2.34)], ALL [1.43 (0.94–2.19)], AML [2.37 (1.10–5.12)] and any cancer [1.33 (1.09–1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes. Conclusions Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.

PURPOSE Primary care physicians have an important role in encouraging adequate cancer screening. Disparities in cancer screening by socioeconomic status (SES) may affect presentation stage and cancer survival. This study aimed to examine whether breast, colorectal, and cervical cancer screening rates in women differed by SES and age, and whether screening rates and SES disparities changed after introduction of a primary care–based national quality indicator program. METHODS This repeated cross-sectional study spanning 2002-2017 included all female Israeli residents in age ranges appropriate for each cancer screening assessed. SES was measured both as an individual-level variable based on exemption from copayments and as an area-level variable using census data. RESULTS In 2017, the most recent year in the study period, screening rates among 1,529,233 women were highest for breast cancer (70.5%), followed by colorectal cancer (64.3%) and cervical cancer (49.6%). Women in the highest area-level SES were more likely to undergo cervical cancer screening compared with those in the lowest (odds ratio = 3.56; 99.9% CI, 3.47-3.65). Temporal trends showed that after introduction of quality indicators for breast and colorectal cancer screening in 2004 and 2005, respectively, rates of screening for these cancers increased, with greater reductions in disparities for the former. The quality indicator for cervical cancer screening was introduced in 2015, and no substantial changes have occurred yet for this screening. CONCLUSIONS We found increased uptake and reduced socioeconomic disparities after introduction of cancer screening indicators. Recent introduction of a cervical cancer screening indicator may increase participation and reduce disparities, as has occurred for breast and colorectal cancer screening. These findings related to Israel’s quality indicators program highlight the importance of primary care clinicians in increasing cancer screening rates to improve outcomes and reduce disparities.

Among the challenges presented by the SARS-CoV2 pandemic are those related to balancing societal priorities with averting threats to population health. In this exceptional context a group of Israeli physicians and public health scholars (multidisciplinary academic group on children and coronavirus [MACC]) coalesced, examining the role of children in viral transmission and assessing the necessity and consequences of restricted in-class education. Combining critical appraisal and analytical skills with public health experience, MACC advocated for safe and monitored school re-opening, stressing the importance of education as a determinant of health, continuously weighing this stance against evolving COVID-19-risk data. MACC’s activities included offering research-based advice to government agencies including Ministries of Health, Finance, and Education. In a setting where government bodies were faced with providing practical solutions to both decreasing disease transmission and maintaining society’s vital activities, and various advisors presented decision-makers with disparate views, MACC contributed epidemiological, clinical and health policy expertise to the debate regarding school closure as a pandemic control measure, and adaptations required for safe re-opening. In this paper, we describe the evolution, activities, policy inputs and media profile of MACC, and discuss the role of academics in advocacy and activism in the midst of an unprecedented public health crisis. A general lesson learned is that academics, based on the rigor of their scientific work and their perceived objectivity, can and should be mobilized to pursue and promote policies based on shared societal values as well as empiric data, even when considerable uncertainty exists about the appropriate course of action. Mechanisms should be in place to open channels to multidisciplinary academic groups and bring their input to bear on decision-making.

To investigate the effect of birth weight (BW) and maternal pre-pregnancy BMI (mBMI) on blood pressure (BP) in adolescence. A Population-based cohort of 11,729 births in Jerusalem during 1974–1976, with archival data on maternal and birth characteristics was performed. Measurements at age 17 were assessed and linear regression models were used to evaluate the associations of birth characteristics with BP outcomes. BW was inversely associated with both systolic (SBP) and diastolic (DBP) BP at age 17 (SBP: B = − 0.829, p = 0.002; DBP: B = − 0.397, p = 0.033). The interaction term between BW and weight at age 17 was significant for DBP (p = 0.017) and pulse pressure (p = 0.005). mBMI yielded significant positive associations with BP, independent of BW. Our findings indicate that there are at least two distinct pathways linking early life characteristics with subsequent BP: Intrauterine growth, as reflected by BW and other genetic or environmental factors, reflected by mBMI and maternal education, contribute to offspring adolescent BP. These results warrant replication in other birth cohorts and underline the need to explore specific mechanisms that account for these associations.

Oral anticoagulants (AC) and antiplatelet (AP) agents are increasingly prescribed to prevent and treat acute and chronic thrombotic conditions. The direct oral anticoagulants (DOAC), a newer class of AC, raise concerns in the trauma setting. Our study aims to compare the mortality rates and other outcomes among adult trauma patients based on pre-admission AC/AP status. We conducted a retrospective cohort study of a prospectively collected database of trauma patients previously on DOAC, warfarin, aspirin or clopidogrel. A matched control group of trauma patients not receiving AC/AP was used for comparison. Our primary endpoint was in-hospital mortality according to antithrombotic medication class. Secondary endpoints included length of stay (LOS), intensive care unit (ICU) admission, need for blood transfusion, and discharge to a dependent setting. Univariate and multivariate analyses were conducted. There were 996 exposed patients and 234 controls, with no major clinically significant difference among study groups in terms of gender, injury site, injury severity, mechanism, and comorbidities. The mortality rates were 2.14% (control, 5/234), 2.88% (DOAC, 3/104), 3.34% (aspirin, 17/509), 7.63% (warfarin, 18/236), 9% (clopidogrel, 8/89), and 13.79% (aspirin + clopidogrel, 8/58) (p

BackgroundUnder the ‘Choosing Wisely’ (CW) framework, professional organisations internationally have advocated limiting imaging for asymptomatic patients following curative cancer therapy, based on limited value and high cost. F18-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) was widely adopted locally for surveillance lymphoma imaging after 2004.ObjectivesPrior to ratification of a local CW recommendation to limit surveillance imaging in lymphoma, we aimed to assess: (A) performance characteristics of surveillance FDG-PET/CT; (B) rates, clinical consequences and costs of false positives (FP); and (C) patients and professionals’ attitudes towards overuse.MethodsMixed methods (quantitative and qualitative) study. We analysed surveillance FDG-PET/CT results of two patient cohorts (n1=215 Hodgkin lymphoma and non-Hodgkin lymphoma; n2=203 Hodgkin lymphoma only). FPs were defined by negative biopsy or clinical follow-up. We held focus group discussions and in-depth interviews eliciting attitudes of 26 patients and 11 clinicians, respectively.ResultsFPs were observed in 25.1% (95% CI 20.5 to 30.5) per scan—cohort 1, and 41.7% (95% CI 37.9 to 45.6) per patient—cohort 2, engendering frequent additional testing. Specific characteristics and location of findings altered the FP rate. The estimated cost per relapse detected was $50 000 (cohort 2). Patients sought reassurance via surveillance imaging, which they considered highly accurate, yet stressful. Aware of radiation risks, they were largely unconcerned about consequences of FPs. Confidence in the treating physicians was an important factor in patients’ acceptance of forgoing imaging. Clinicians, frequently under patient pressure to order imaging, generally believed that it did not affect prognosis (with important exceptions), welcomed professional guidelines, but rejected regulatory restrictions on its use.ConclusionAcceptance of CW recommendations to limit overuse may be enhanced by quantitative data on consequences and costs of surveillance imaging, supplemented by qualitative data on patient and physician attitudes.

Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose–responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0–24 h) and childhood cancer risk. In a restricted analysis of 154,121 individuals who experienced third trimester photoperiods exclusively within the 8–16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84–0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse [“protective”] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8–16-h set of the total study population. Limited statistical power impeded the investigation of risks with individuals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.

Importance Patients with diabetes are known to be at increased risk for infections including severe coronavirus disease 2019 (COVID-19) but the relationship between COVID-19 severity and specific pre-infection glucose levels is not known. Objective To assess the differential effects of pre-infection glucose levels on the risk for severe COVID-19 amongst patients with and without diabetes. Design Population based historical cohort study. Setting National state-mandated HMO. Patients All adult patients with a positive SARS-COV2 test between March-October 2020. Exposure Recent fasting blood glucose (FBG) and glycated hemoglobin (HBA1C), age, gender, body mass index (BMI) and diagnoses of diabetes, hypertension, ischemic heart disease. Outcome Risk for severe COVID-19, defined as resulting in ≥10 hospitalization days, ICU admission or death. Results 37,121 patients with a positive SARS-COV2 test were identified; 707 defined as severe (1.9%). Unadjusted risk factors for severe disease were age (OR = 1.1 for every year increase; 95% CI 1.09–1.11, p < 0.001), male gender (OR = 1.34, 95% CI 1.06–1.68, p = 0.012); BMI (OR = 1.02 for 1 kg/m2 increase, 95% CI 1.00–1.04, p = 0.025). Controlling for these factors, we found an association between pre-infection FBG and the risk of severe COVID-19, with a differential effect in patients with and without a diagnosis of diabetes. For patients without diabetes, elevated FBG in the pre-diabetes range (106–125 mg/dl) was associated with severe COVID-19 (OR 1.55 95% CI 1.04–2.26 p = 0.027). For patients with a diagnosis of diabetes, we found a J-shaped association between pre-infection glucose control and the risk for severe COVID-19 where the lowest risk for was for patients with FBG 106–125 mg/dl; the risk increased with higher pre-infection glucose levels but strikingly also for patients with a low pre-infection FBG ( Conclusions and relevance Elevated pre-infection blood glucose is a risk factor for severe COVID-19 even in non-diabetics. For patients with a diagnosis of diabetes both high as well as low pre-infection glucose levels are risk factors for severe COVID-19. Further research is required to assess whether these associations are causal, but we believe these findings can already have clinical implications for COVID-19 risk assessment and stratification.

Background While health promotion initiatives are common, too little is known about their quality, impact and sustainability. Fragmentation between sectors exists and programme evaluation initiatives lack consistency, making comparison of outcomes challenging. Methods We used a ‘snowball’ methodology to detect health promotion programmes (HPPs) in the Municipality of Jerusalem, excluding those in schools. The European Quality Instrument for Health Promotion (EQUIHP) was adapted and used to examine programme quality. The tool was pre-tested among stakeholders, and translated into Hebrew and Arabic between March and December 2017. Trained research assistants collected information on four domains using in-person interviews: (i) compliance with international principles of HPPs, (ii) development and implementation, (iii) project management and (iv) sustainability of programmes. Results Overall, 93 programmes, including 33 670 participants, were ascertained and evaluated. The majority of HPPs (54.8%) addressed nutrition and physical activity, with 58.1% targeting the non-orthodox Jewish population and 68.8% aimed at both sexes. Cronbach’s alpha scores were 0.968 for the entire EQUIHP tool and 0.802, 0.959, 0.918 and 0.718 for the subdomains of Framework, Project Development, Project Management and Sustainability, respectively. Median domain scores were 0.83, 0.61, 0.76 and 0.75. Median score of the entire tool was 0.67. HPPs operated by the Municipality scored lower than those of non-governmental organizations and health providers/organizations in every domain except for Project Management. Conclusion A systematic city-wide evaluation of HPPs is feasible and uncovers strengths and weaknesses, including sustainability and variability by programme provider. Academic-community partnerships may assist planning and improving HPPs in the city.

Background: The success of Helicobacter pylori (H. pylori) eradication depends on several host and treatment factors. Serum vitamin D levels may be associated with H. pylori infection and eradication rates. We investigated the association between vitamin D and H. pylori infection and eradication, using a large electronic database based on medical records from a population-based health maintenance organization. Methods: Data regarding adults who underwent H. pylori testing and had vitamin D measurements within one month of H. pylori testing were collected. H. pylori infection was ascertained using urea breath or stool antigen tests. A negative H. pylori test following a positive result implied eradication. Multivariate regression models were constructed to assess associations between H. pylori infection, eradication, and vitamin D. Results: Among 150,483 members who underwent H. pylori testing from 2009 to 2018, 27,077 (18%) had vitamin D measurements. Vitamin D levels were inversely associated with H. pylori infection, p &lt, 0.001. The odds of a positive H. pylori test were 31% higher among patients with vitamin D levels &lt, 20 ng/mL, compared with those with levels &ge, 20 ng/mL (OR 1.31, 99% CI 1.22&ndash, 1.4, p &lt, 0.001). Purchase of vitamin D supplements was associated with a negative subsequent H. pylori test (p &lt, 0.001). Mean vitamin D levels were moderately higher in those with successful vs. failed H. pylori eradication (19.34 &plusmn, 9.55 vs. 18.64 &plusmn, 9.61, p &lt, 0.001). Conclusions: Vitamin D levels are associated with H. pylori infection. Increased vitamin D levels are associated with successful H. pylori eradication. Vitamin D may have a role in H. pylori eradication.

Treated wastewater (TWW) is increasingly used for agricultural irrigation, especially in arid and semi-arid regions. Carbamazepine is among the most frequently detected pharmaceuticals in TWW. Moreover, its uptake and accumulation have been demonstrated in crops irrigated with TWW. A previous controlled trial found that urine concentrations of carbamazepine were higher in healthy volunteers consuming TWW-irrigated produce as compared to freshwater-irrigated produce. The aim of the current study was to assess whether carbamazepine is quantifiable in urine of Israelis consuming their usual diets and whether concentrations vary according to age, personal characteristics and diet. In this cross-sectional study, we recruited 245 volunteers, including a reference group of omnivorous healthy adults aged 18–66; pregnant women; children aged 3–6 years; adults aged >75 years; and vegetarians/vegans. Participants provided spot urine samples and reported 24-hour and “usual” dietary consumption. Urinary carbamazepine levels were compared according to group, personal characteristics, health behaviors, and reported diet. Carbamazepine was detectable (≥1.66 ng/L) in urine of 84%, 76%, 75.5%, 66%, and 19.6% of the reference group, vegetarians, older adults, pregnant women, and children, respectively. Quantifiable concentrations (≥5.0 ng/L) of carbamazepine were found in 58%, 46%, 36.7%, 14%, and 0% of these groups, respectively (p = 0.001 for comparison of proportions across groups). In adults, higher carbamazepine concentrations were significantly associated (p

Objectives To assess time trends in colorectal cancer screening uptake, time-to-colonoscopy completion following a positive fecal occult blood test and associated patient factors, and the extent and predictors of longitudinal screening adherence in Israel. Setting Nation-wide population-based study using data collected from four health maintenance organizations for the Quality Indicators in Community Healthcare Program. Methods Screening uptake for the eligible population (aged 50–74) was recorded 2003–2018 using aggregate data. For a subcohort (2008–2012, N = 1,342,617), time-to-colonoscopy following a positive fecal occult blood test and longitudinal adherence to screening guidelines were measured using individual-level data, and associated factors assessed in multivariate models. Results The annual proportion screened rose for both sexes from 11 to 65%, increasing five-fold for age group 60–74 and >six-fold for 50–59 year olds, respectively. From 2008 to 2012, 67,314 adults had a positive fecal occult blood test, of whom 71% eventually performed a colonoscopy after a median interval of 122 (95% confidence interval 110.2–113.7) days. Factors associated with time-to-colonoscopy included age, socioeconomic status, and comorbidities. Only 25.5% of the population demonstrated full longitudinal screening adherence, mainly attributable to colonoscopy in the past 10 years rather than annual fecal occult blood test performance (83% versus 17%, respectively). Smoking, diabetes, lower socioeconomic status, cardiovascular disease, and hypertension were associated with decreased adherence. Performance of other cancer screening tests and frequent primary care visits were strongly associated with adherence. Conclusions Despite substantial improvement in colorectal cancer screening uptake on a population level, individual-level data uncovered gaps in colonoscopy completion after a positive fecal occult blood test and in longitudinal adherence to screening, which should be addressed using focused interventions.

IntroductionScarce research is available regarding the association between interbirth intervals (IBI) and long-term maternal health outcomes, particularly cardiovascular disease (CVD) mortality. We aimed to assess whether IBIs were associated with all-cause, CVD-related and cancer-related mortality.MethodsWe conducted a cohort study in the setting of the Jerusalem Perinatal Study. Women with at least two consecutive singleton live births in 1964–1976 (N=18 294) were followed through 2016. IBIs were calculated as the interval between women’s first and second cohort birth. We estimated associations between IBIs and mortality using Cox’s proportional hazards models, adjusting for age, parity, maternal education, maternal origin and paternal socioeconomic status. Date of last menstrual period was available for a subset of women. We assessed the interpregnancy interval (IPI) for these women and compared the models using IPI and IBI.ResultsDuring 868 079 years of follow up (median follow-up: 49.0 years), 3337 women died. Women with IBIs ConclusionOur results support the WHO recommendations for IPIs of ≥24 months and add additional evidence regarding long-term CVD mortality.

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at

Chronic hepatitis C virus (HCV) infection, associated with severe liver disease and cancer, affects 70 million people worldwide. New treatments with direct-acting-antivirals offer cure for about 95% of affected individuals; however, treatment costs may be prohibitive in both the poorest and richest nations. Opting for cure may require sacrificing essential household assets. We highlight the financial dilemmas involved, drawing parallels between Ethiopia and the United States, countries where universal health coverage does not yet exist. The World Health Organization (WHO) declaration for HCV eradication by 2030 will only become reality if universal access to efficacious and affordable treatment is guaranteed for everyone.

Previous studies and meta-analyses addressing COVID-19 in patients with hematological malignancies (HM) have reported dramatically high mortality rates of up to 34% [Vigenthira 2020, Garcia-Suarez 2020, Sharafeldin 2021]. These studies, however, were strongly biased towards hospitalized patients, and poorly represented patients who experienced a milder course of COVID-19, not requiring hospitalization. Jerusalem and its metropolitan area, comprising of over 1.3 million inhabitants, was the epicenter of Israel's COVID-19 crisis, with over 200,000 cases. Hadassah Medical Center, one of only two tertiary centers serving this multi-ethnic population, houses a Hematology Department that includes inpatient services, a hematopoietic stem cell transplant (HSCT) center, day care services and in-campus outpatient clinics. From February 20 th, 2020, we tracked patients with confirmed COVID-19 reporting to their treating hematologists while being hospitalized due to COVID-19, at routine visits to the hematology services, or remotely via phone or email communication. This assured the representation of COVID-19 cases of various clinical severities. Data were collected retrospectively and included demographics, comorbidities, hematological diagnoses and treatments, course of COVID-19 and, importantly, source of infection. Univariate and multivariate analyses were used to assess association between prognostic factors and outcomes including hospitalization, severe COVID-19 (per updated WHO criteria) and critical COVID-19, defined as a composite of ICU admission and mortality. Almost all the patients in this series were diagnosed prior to their vaccination. To the best of our knowledge, this is the largest single center series of HM patients with COVID-19 reported to date. Our series included 183 patients. Median age was 62.5 years, 57% were men, and 72% had at least one comorbidity. The most frequent hematological diagnoses were indolent lymphoma and CLL (40%), aggressive lymphoma (20%) and multiple myeloma (19%). At the time of COVID-19 diagnosis, 41% of the patients were receiving systemic anti-neoplastic treatment (excluding TKIs for CML and hydroxyurea for MPN), and 16% had undergone a previous allogeneic or autologous HSCT. Overall mortality, severe COVID-19, and hospitalization rates in the entire group were 9.8%, 14.2% and 32%, respectively, remarkably lower than in previous reports. Of the patients not receiving anti-neoplastic treatment, mortality and severe COVID-19 rates were comparable to those of the age-matched general population according to the Israeli Ministry of Health database [Table 1]. Consistent with previous studies, ischemic heart disease (IHD), dyslipidemia, chronic kidney disease, smoking and hypertension, as well as age and active anti-neoplastic treatment, each emerged as a risk factor significantly associated with hospitalization due to COVID-19 [Fig. 1, Table 2]. IHD, smoking, age and active treatment remained significant in multivariate analysis. Age and active treatment as well as ≥4 comorbidities were significantly associated with critical COVID-19. Interestingly, we observed a strong association between the number of prior anti-neoplastic treatment lines and critical COVID-19. Neither history of HSCT nor treatment with monoclonal antibodies were associated with COVID-19 outcomes. Notably, we did not detect any patient that contracted COVID-19 within the Hematology Department services, both inpatient and outpatient. Taken together, we present a different COVID-19 severity landscape in patients with HM as compared to previous observations. While active treatment was significantly associated with COVID-19 hospitalization and mortality, these rates were remarkably lower than previously reported. Despite harboring various degrees of immune suppression, patients with stable or indolent diseases not receiving active treatment appeared to be at a risk comparable to that of the age-matched general population, which depended largely on age and comorbidities. Routine preventive measures including symptom questioning, masks, and social distancing in both our inpatient and outpatient services provided a COVID-19-safe environment, obviating the need for changes in treatment schedules or assignment. These findings may have important consequences for future management of patients with HM in COVID-19 affected regions. Figure 1 Figure 1. Disclosures Lavie: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Fees for lectures; Roche: Other: Fees for lectures; Novartis: Other: Fees for lectures; Takeda: Consultancy. Goldschmidt: AbbVie: Consultancy, Research Funding.

Objective To evaluate associations between using complementary medical therapies (CMTs) and embryologic and clinical outcomes of in vitro fertilization (IVF). Methods The present prospective questionnaire-based cohort study enrolled women aged 18–44 years undergoing their first, second, or third IVF cycle using their own oocytes at a large IVF clinic in Israel between February 1, 2013, and July 31, 2015. Clinical and embryologic data were obtained from patient records and patients completed a self-administered questionnaire that included details of any CMTs used to treat infertility. Propensity score matching was used and the proportion of top-quality embryos was compared between CMT users and non-users. Results The study enrolled 400 participants and 134 (33.5%) reported using CMT to treat infertility. In an unmatched analysis, reduced endometrium thickness was observed among CMT users (P=0.020); differences were not observed for embryologic or other clinical parameters. Following propensity score matching, reduced endometrial thickness (P=0.046), and a lower proportion (P=0.046) and number (P=0.040) of top-quality embryos were observed among CMT users in comparison with patients who did not use CMTs. Conclusions Using CMTs was associated with inferior clinical and embryologic outcomes; using CMTs during IVF treatment could contribute to adverse outcomes. This article is protected by copyright. All rights reserved.

Summary This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18–60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced-HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13–119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients.

Objective To develop, apply, and evaluate, a novel web‐based classifier for screening for Parkinson disease among a large cohort of search engine users. Methods A supervised machine learning classifier learned to distinguish web users with self‐reported Parkinson's disease from controls based on their interactions with a search engine (Bing, Microsoft). It was then applied to groups of web users with low or high risk for actual Parkinson's disease. Textual content of web queries was used to sort surfers into the different risk groups, but not for classifying users as negative or positive for Parkinson's disease. Disease detection was unsolicited. Researchers did not have access to any identifying data on users. Results Applying the classifier (with an estimated positive predictive value of 25%) resulted in 17,843/1,490,987 (1.2%) web users over the age of 40 years screened positive for Parkinson's disease. This percentile was higher in at‐risk groups (Fisher exact P

Objective To summarize the published evidence regarding the association between maternal infection during pregnancy and childhood leukemia. Study design In this systematic review and meta-analysis (PROSPERO number, CRD42018087289), we searched PubMed and Embase to identify relevant studies. We included human studies that reported associations of at least one measure of maternal infection during pregnancy with acute lymphoblastic leukemia (ALL) or all childhood leukemias in the offspring. One reviewer extracted the data first using a standardized form, and the second reviewer independently checked the data for accuracy. Two reviewers used the Newcastle-Ottawa Scale to assess the quality of included studies. We conducted random effects meta-analyses to pool the ORs of specific type of infection on ALL and childhood leukemia. Results This review included 20 studies (ALL, n = 15; childhood leukemia, n = 14) reported in 32 articles. Most (>65%) included studies reported a positive association between infection variables and ALL or childhood leukemia. Among specific types of infection, we found that influenza during pregnancy was associated with higher risk of ALL (pooled OR, 3.64; 95% CI, 1.34-9.90) and childhood leukemia (pooled OR, 1.77; 95% CI, 1.01-3.11). Varicella (pooled OR, 10.19; 95% CI, 1.98-52.39) and rubella (pooled OR, 2.79; 95% CI, 1.16-6.71) infections were also associated with higher childhood leukemia risk. Conclusions Our findings suggest that maternal infection during pregnancy may be associated with a higher risk of childhood leukemia.

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case–control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (

Objectives. To assess whether there are shared exposures associated with Sjogren’s syndrome (SS), dry eye syndrome (DES), and B-cell non-Hodgkin lymphoma (B-NHL), in order to determine whether they are etiologically related. Methods. In a clinic-based case-control study, 702 participants (91 SS, 120 DES, 211 (age and sex frequency-matched) controls, and 280 B-NHL cases) were recruited and interviewed regarding exposures, medical history, and family history. Results. Female predominance was noted in SS (ratio 9.2 : 1). Eye dryness was severest in SS compared to DES and controls (P<0.001). Compared to controls, alcohol consumption was inversely associated with NHL, DES, and SS (odds ratio OR=0.47, 95% confidence interval (CI): 0.31-0.71; OR=0.54, 95% CI: 0.33-0.88; and OR=0.26, 95% CI: 0.14-0.49, respectively), while a previous history of infection requiring hospitalization was positively associated with all three conditions: NHL (OR=1.92; 95% CI: 1.23-2.99), DES (OR=3.29; 95% CI: 1.97-5.47), and SS (OR=4.74; 95% CI: 2.66-8.44). NHL patients were more likely to report first-degree relatives with hematologic cancer, while having first-degree relatives with an autoimmune disease (AID) was associated with SS (OR=5.25; 95% CI: 2.59-10.63) and DES (OR=3.55; 95% CI: 1.83-6.91) compared to controls. Conclusions. Some exposures are associated with all three conditions (such as an inverse association with alcohol consumption and a positive association with serious past infection), while a family history of AID appears to be shared by DES and SS, but not NHL subjects. Shared risk factors for all three conditions indicate possible mutual etiological pathways.

Objectives To compare hematologic and serological parameters among patients with Sjogren’s syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. Methods In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the “Immunodot” qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). Results Among DES patients, only 2% (95%CI: 0.36–6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P Conclusions Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

To evaluate associations between the use of complementary medicine, quality of life (QoL), and lifestyle habits among women undergoing in vitro fertilization (IVF).In a cross-sectional study, women aged 18-44 years undergoing an IVF cycle at a large IVF center in Israel between February 1, 2013 and April 30, 2015 were invited to complete a self-administered questionnaire. Patients who reported using of at least one complementary medicine intervention to treat infertility prior to IVF treatment were considered complementary-medicine users. Fertility QoL and lifestyle behaviors were compared between complementary-medicine users and non-users with the FertiQoL tools.Of 381 patients eligible to participate in the study, 323 completed the questionnaire; 110 (34.1%) participants were complementary-medicine users. Complementary-medicine users demonstrated higher scores for the FertiQol relational domain (P=0.005) and lower scores for the social domain (P=0.010). Complementary-medicine users reported greater utilization of psychosocial support (P0.001), and higher rates of physical activity (P=0.004) and consulting with dietitians (P=0.050).Users of complementary medicine reported increased relational and lower social QoL, increased use of psychosocial support, and favorable healthy-lifestyle habits. Actively inquiring about the lifestyle habits and QoL of patients experiencing infertility could be useful in identifying patients who could benefit from psychosocial interventions or lifestyle recommendations.

Presenting symptoms of multiple myeloma (MM) are vague and nonspecific. Early detection poses a diagnostic challenge in primary care. We assessed whether clinical and laboratory data could provide early clues to MM diagnosis and whether time to detection affects survival.A retrospective population-based study, including 110 men and women diagnosed with MM between 2002 and 2011, and matched cancer-free controls presenting with back pain. Clinical and laboratory data were extracted from medical records for the 2-year period prior to diagnosis of MM/back pain complaint.During the two years prior to diagnosis 64 (58%) of MM patients complained of back pain, and 37 (34%) suffered from fatigue or weight loss. Case-control comparisons did not reveal any significant differences in the number of pain complaints or infections in the two-year prediagnostic period. However, fatigue or weight loss, anemia, elevated ESR and creatinine (p0.001 for all) occurred more frequently in MM patients than controls and were confirmed as independent predictors in multivariated analysis. TTD did not impact stage at diagnosis, survival, or mortality.Back pain accompanied by fatigue, weight loss or abnormal lab results should raise a "red flag" warning of MM. Nonetheless, we did not find evidence that TTD influences the initial stage or the prognosis of MM.

In recent years, anti-CD20 antibodies have been increasingly used to treat lymphoproliferative and immune disorders. Chronic viral infections are infrequently reported in patients receiving these therapies. Enteroviral infection can cause life-threatening meningoencephalitis and other systemic chronic syndromes in immune deficient patients. We describe the clinical courses and outcomes of 6 patients from 2 tertiary care institutions who developed chronic enteroviral infection with neurological manifestations, after combined chemoimmunotherapy with rituximab for B-cell lymphoma. We review the literature that includes 10 sporadic reported cases of chronic enteroviral meningoencephalitis attributed to rituximab therapy. It is a rare disease, and its diagnosis is often elusive. We propose that low immunoglobulin G levels are the main risk factor for developing chronic enteroviral infection and emphasize the need for a high index of suspicion, early diagnosis, and intervention in this iatrogenic and potentially fatal complication.

Outcomes in primary mediastinal B cell lymphoma (PMBL) improved with the introduction of dose intense treatments, consolidation radiotherapy and rituximab. DA-EPOCH-R, which omits radiotherapy has been adopted with worldwide enthusiasm, despite lack of proven superiority in randomized trials. We aimed to evaluate the course and outcome of PMBL using an alternative intensive rituximab-containing regimen, RCHOP-RICE. We also evaluated the prognostic value of 18FDG-PET-CT (PET-CT). We reviewed the clinical, laboratory and imaging data of PMBL patients receiving 1st-line treatment in Hadassah Medical Center between 8/2002 and 10/2014. Of 47 PMBL patients, 24 (51 %) were treated with RCHOP-RICE and 23 (49 %) with other protocols. Overall, the 5-year progression-free survival was 93 % and the overall survival was 98 % (87 and 100 %, respectively, for the RCHOP-RICE regimen). Patient characteristics and treatment toxicities were balanced among protocols. A mean of 11.1 ± 1.3 hospitalization days/patient were needed to administer RCHOP-RICE regimen compared to 37 ± 2 days/patient for DA-EPOCH-R (n = 2). Radiotherapy was given to 3 patients (12 %) treated with RCHOP-RICE compared to 18 patients (78 %) treated with other protocols (p

Background Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for Methods Eligibility criteria, follow‐up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. Results Currently, six cohorts recruited over six decades (1950s‐2000s) contribute data on 388 120 mother‐child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother‐child pairs within 5 years. Harmonised data currently includes over 20 “core” variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. Conclusions The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case‐control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

Associations of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) with non-Hodgkin lymphoma are controversial. We compared serum levels of 6 OC pesticides and 38 PCBs in Israeli Jews (IJ) and Palestinian Arabs (PA) and assessed possible associations with B-cell non-Hodgkin lymphoma (B-NHL). Ninety B-NHL cases (50 IJ and 40 PA) and 120 controls (65 IJ and 55 PA) were included. Median concentrations of analytes in controls were compared across ethnic groups using quantile regression, adjusting for age and sex. We used logistic regression to derive odds ratios (OR) and 95% confidence intervals (CI) for detectable analytes and B-NHL, adjusting for age, ethnic group, faming and body mass index. Median values of PCBs and dichlorodiphenyldichloroethylene (DDE) were higher in IJ vs PA controls (P = 0.0007), as were several PCBs (74, 99, 118, 138, 146, 153, 156, 163, 170, and 180). Overall, OC pesticide and PCB exposures were comparable with reports from high-income countries. B-NHL was associated with PCB 146 (OR 1.70, 95% CI: 1.02, 2.83), PCB 156 (OR 1.75, 95% CI: 1.06, 2.89), and high-chlorinated PCBs (OR 1.55, 95% CI: 1.00, 2.40) in all study subjects. These associations were robust in quantile as well as sensitivity analyses. An association of DDE with B-NHL was noted in PA (OR 1.72, 95% CI: 1.07, 2.77), but not in IJ (OR 0.87, 95% CI: 0.59, 1.27). Although high-chlorinated PCB concentrations did not indicate high exposure levels, our findings indicate that B-NHL may be associated with this exposure.

Introduction Vocal problems among teachers are considered a common professional hazard and a significant source of disability, leading to reductions in quality-of-life and professional capacities. Factors related to fitness-for-work reductions were not evaluated so far. Recommendations for voice-therapy, rest and microphone use are common interventions in occupational medicine aimed at preserving the working capability of these teachers and reducing work disability. Research on the impact of such interventions on employment capacity is lacking. The aims of the study regarding dysphonic teachers referred to occupational medicine clinic: evaluate employment outcomes following voice-therapy, voice rest and microphone use, and identify other predictors to limitations in fitness-for-work. Methods Teachers who were first referred to occupational medicine clinic due to voice disorders between 1/2007 and 12/2012 were followed-up. Data were collected from medical records and from interviews conducted in 2014. Logistic regression models were utilised to assess associations between interventions and other covariates, and employment outcomes. Survival analysis was performed to evaluate association between undergoing voice-therapy and length of retained fitness-for-work. Results A sample of 153 dysphonic teachers comprised the prospective study cohort, which was followed for 2–8 years. Thirty-four (22.2%) suffered declines in working capabilities. Voice-therapy was protective against such declines [OR=0.05(0.01–0.27)], in contrast to voice rest and microphone use. Compliance with voice-therapy recommendation was less than 50%. Most of declines in fitness-for-work among non-compliant teachers occurred within 20 months after referral. Other predictors were associated with work fitness reduction. Discussion Voice-therapy, especially when instituted early, is the strongest predictor for retaining fitness-for-work among dysphonic teachers. Pilot study with employers is warranted to estimate compliance and economic feasibility of preventive measures including voice-therapy aimed at reducing disability and preserving work capacities.

Background Israel is one of the few countries that have a national program for quality assessment of community healthcare. We aimed to evaluate whether improved performance in diabetes care was associated with improved health of diabetic patients on a national level. Methods We conducted a nationwide ecological study estimating improvements in diabetes-related quality indicators and health outcomes. We estimated both correlations between composite measures of diabetes-related quality indicators and selected outcomes, and assessed through a joinpoint analysis whether trends in selected outcomes changed 4 years after the inception of the national program. Results Between 2002 and 2010, the prevalence of diabetes in Israeli adults increased from 4.8% to 7.4%. During these years, an improvement was noticed in most quality indicators (from 53% to 75% for the composite score). Declines were noted in rates of blindness, diabetes-related end-stage kidney disease, lower limbs amputations and diabetes-related mortality. Significant accelerations in decline were noted for amputations in men and diabetes-related mortality in both Arab men and women 4 years after the inception of the national program. Conclusion This study suggests that Israel’s national program for quality indicators in diabetes care in the community has probably had a significant impact on the health status of the whole population and may have contributed to narrowing gaps in life expectancy between Israeli Jews and Arabs. Future studies based on individual-level data are needed to confirm these results. Electronic supplementary material The online version of this article (10.1186/s13584-018-0206-3) contains supplementary material, which is available to authorized users.

PURPOSE The aim of this study was to examine the prevalence of urinary incontinence (UI) among parous women of child-bearing age and compare their level of knowledge regarding UI to those women without the condition. METHODS A convenience sample of women aged 20 to 50 years who had given birth at least once completed questionnaires regarding (1) demographic information, (2) knowledge of UI (PIKQ-Prolapse and Incontinence Knowledge Quiz and PIKQ+), and (3) prevalence of UI (ICIQ-UI questionnaire-International Consultation on Incontinence Questionnaire-Urinary Incontinence short form). Women who were pregnant or 3 months or less postpartum were excluded from the analysis of the ICIQ-UI. RESULTS Three hundred twenty-three women, representing 89.7% of those approached, participated in the study. Their mean age was 35.3 ±5.0 years (mean ± SD), all completed the knowledge questionnaire while 260 (80.5%) completed the UI questionnaire. Eighty-three (31.9%) suffered from UI, and most (67.5%) were between 31 and 40 years of age. Participants' level of knowledge about UI was found to be moderate (mean = 7.37 ± 3.6) on the PIKQ+. Knowledge level was correlated with age (P = .017) and with higher levels of education (P < .001). There was a significantly higher level of UI knowledge (PIKQ+ scores) among women with UI (mean = 8.6; SD = 3.01) as compared to those who did not report UI (mean = 7.6; SD =±3.75; P < .001). CONCLUSION Approximately one-third of parous women aged 20 to 50 years reported UI. Knowledge related to the condition tends to be moderate, increasing with higher age and education.

Although exposure to traffic-related air pollution has been reported to be associated with respiratory morbidity in children, this association has not been examined in Israel. Jerusalem is ranked among the leading Israeli cities in transport-related air pollution. This case–control study examined whether pediatric hospitalization for respiratory diseases in Jerusalem is related to residential exposure to traffic-related air pollution. Cases (n = 4844) were Jerusalem residents aged 0–14 years hospitalized for respiratory illnesses between 2000 and 2006. These were compared to children admitted electively (n = 2161) or urgently (n = 3085) for non-respiratory conditions. Individual measures of exposure included distance from residence to nearest main road, the total length of main roads, traffic volume, and bus load within buffers of 50, 150, and 300 m around each address. Cases were more likely to have any diesel buses passing within 50 m of their home (adjusted odds ratios = 1.16 and 1.10, 95% confidence intervals 1.04–1.30 and 1.01–1.20 for elective and emergency controls, respectively). Our findings indicated that older girls (5–14) and younger boys (0–4) had increased risks of respiratory hospitalization, albeit with generally widened confidence intervals due to small sample sizes. Our results add to the limited body of evidence regarding associations between diesel exhaust particles and respiratory morbidity. The findings also point to possible differential associations between traffic-related air pollution and pediatric hospitalization among boys and girls in different age groups.

Although autoimmune diseases (AIDs) are known to predispose to non-Hodgkin lymphoma (NHL), their association with NHL prognosis has rarely been investigated. We examined associations between autoimmunity and B-cell NHL onset by comparing AID history (determined by self-report and medication review and supplemented by chart review where possible) among 435 adult B-NHL patients in Hadassah-Hebrew University Medical Center, diagnosed 2009-2014, and 414 age-and-sex frequency-matched controls. We examined AIDs as a whole, B- and T-cell–mediated AIDs, and autoimmune thyroid diseases. Among cases, we used Kaplan-Meier and Cox regression models to assess the association of AID with overall survival and relapse-free survival, adjusting for prognostically important patient and disease characteristics such as Ki67% staining, International Prognostic Index, rituximab treatment, and histological subgroup. Autoimmune diseases were associated with B-NHL (odds ratio [OR] = 1.95; 95% confidence interval (CI), 1.31-2.92), especially AIDs mediated by B-cell activation (OR = 5.20; CI, 1.90-14.3), which were particularly associated with marginal zone lymphoma (OR = 19.3; CI, 4.59-80.9). We found that time to relapse for all B-NHL patients with AIDs was significantly shorter (mean of 49.21 mo [±3.22]) than among patients without AID (mean of 59.74 mo [±1.62]), adjusted hazard ratio [HRadj] = 1.69 (CI, 1.03-2.79). Specifically, in patients with diffuse large B-cell lymphoma, of whom 91.8% had received rituximab, a history of B-cell–mediated AIDs was associated with shorter relapse-free survival and overall survival, HRadj = 8.34 (CI, 3.01-23.1) and HRadj = 3.83 (CI, 1.20-12.3), respectively. Beyond confirming the well-known association between AIDs and B-NHL, we found that AID is an adverse prognostic factor in B-cell lymphoma, associated with a shortened time to relapse, suggesting that there are specific therapeutic challenges in the subgroup of patients suffering from both these diseases. Further work is required to address mechanisms of resistance to standard treatment in the setting of AID-associated B-NHL. In the era of immunotherapy, these findings have particular relevance.

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. Patients with stage I disease are usually treated with radiotherapy (RT). In previous studies, mostly from the pre positron emission tomography-computed tomography (PET-CT) era, the 5 year progression-free survival (PFS) and overall survival (OS) rates of stage I disease were 60-80% and 80-93%, respectively. This study retrospectively evaluated the outcome of stage I FL which was treated with involved field RT in the PET-CT era between 2002 and 2015. Ninety-one patients were enrolled. Five year PFS and OS rates were 73% and 97%, respectively. Relapse occurred in 19 (21%) patients, 74% occurring outside the radiation field. In conclusion, PET-CT staging of clinical stage I FL may contribute to the improved prognosis in patients treated with RT compared to historical cohorts, possibly due to better identification of "genuine" stage I disease.

Medical professionalism refers to attributes, values, behaviors, responsibilities and commitments of physicians that are congruent with the public’s expectations. An international workshop on medical professionalism took place at the Dead Sea, Israel, on December 11–12, 2016. The meeting brought together local medical professionals, physicians and others, as well as international experts, to discuss definitions of professionalism and wrestle with current challenges facing the profession including its perceived status and physician satisfaction, unprofessional behavior and its relation to health care quality and patient safety, and professionalism as a learned competence. Individual medical schools reported on educational efforts to promote professionalism in their curricula. Patient complaints as an improvement mechanism were explored on a national and health plan level. I was found that complaints regarding physician behavior are rare in the Israeli context and need to be dealt with expeditiously at a local level in order to be effective tools for change. The meeting provided a venue to understand local and international strategies and mechanism for regulation and self-regulation, highlighting the role of the Israel Medical Association. A major focus of the meeting was on intergenerational differences in attitude and practice and the necessary adaptation of medicine to the digital age. We provide an overview of the topics addressed, synopsis, evaluation and lessons learned in this first-ever national meeting on medical professionalism in Israel. Electronic supplementary material The online version of this article (doi:10.1186/s13584-017-0144-5) contains supplementary material, which is available to authorized users.

Background There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols. Methods Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given. Results In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38 °C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P = 0.13 and 76%, P = 0.002, respectively) and imipenem (93%, P = 0.004 and 92%, P = 0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days. Conclusion Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients.

Although risk factors for diffuse large B-cell lymphoma (DLBCL) have been suggested, their independent effects, modification by sex, and association with anatomical sites are largely unknown.In a pooled analysis of 4667 cases and 22639 controls from 19 studies, we used stepwise logistic regression to identify the most parsimonious multivariate models for DLBCL overall, by sex, and for selected anatomical sites.DLBCL was associated with B-cell activating autoimmune diseases (odds ratio [OR] = 2.36, 95% confidence interval [CI] = 1.80 to 3.09), hepatitis C virus seropositivity (OR = 2.02, 95% CI = 1.47 to 2.76), family history of non-Hodgkin lymphoma (OR = 1.95, 95% CI = 1.54 to 2.47), higher young adult body mass index (OR = 1.58, 95% CI = 1.12 to 2.23, for 35+ vs 18.5 to 22.4 kg/m(2)), higher recreational sun exposure (OR = 0.78, 95% CI = 0.69 to 0.89), any atopic disorder (OR = 0.82, 95% CI = 0.76 to 0.89), and higher socioeconomic status (OR = 0.86, 95% CI = 0.79 to 0.94). Additional risk factors for women were occupation as field crop/vegetable farm worker (OR = 1.78, 95% CI = 1.22 to 2.60), hairdresser (OR = 1.65, 95% CI = 1.12 to 2.41), and seamstress/embroider (OR = 1.49, 95% CI = 1.13 to 1.97), low adult body mass index (OR = 0.46, 95% CI = 0.29 to 0.74, for18.5 vs 18.5 to 22.4 kg/m(2)), hormone replacement therapy started age at least 50 years (OR = 0.68, 95% CI = 0.52 to 0.88), and oral contraceptive use before 1970 (OR = 0.78, 95% CI = 0.62 to 1.00); and for men were occupation as material handling equipment operator (OR = 1.58, 95% CI = 1.02 to 2.44), lifetime alcohol consumption (OR = 0.57, 95% CI = 0.44 to 0.75, for400 kg vs nondrinker), and previous blood transfusion (OR = 0.69, 95% CI = 0.57 to 0.83). Autoimmune disease, atopy, and family history of non-Hodgkin lymphoma showed similar associations across selected anatomical sites, whereas smoking was associated with central nervous system, testicular and cutaneous DLBCLs; inflammatory bowel disease was associated with gastrointestinal DLBCL; and farming and hair dye use were associated with mediastinal DLBCL.Our results support a complex and multifactorial etiology for DLBCL with some variation in risk observed by sex and anatomical site.

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the fifth most common type of cancer in more developed regions of the world (1). Numerous NHL subtypes with distinct combinations of morphologic, immunophenotypic, genetic, and clinical features are currently recognized (2,3). The incidence of NHL subtypes varies substantially by age, sex, and race/ethnicity (4–7). However, the etiological implications of this biological, clinical, and epidemiological diversity are incompletely understood. The importance of investigating etiology by NHL subtype is clearly supported by research on immunosuppression, infections, and autoimmune diseases, which are the strongest and most established risk factors for NHL. Studies of solid organ transplant recipients and individuals infected with HIV demonstrate that risks are markedly increased for several—but not all—NHL subtypes (8–13). Some infections and autoimmune diseases are associated with a single specific subtype [eg, human T-cell lymphotropic virus, type I (HTLV-I) with adult T-cell leukemia/lymphoma (14), celiac disease with enteropathy-type peripheral T-cell lymphoma (PTCL) (15–17)], whereas others [eg, Epstein–Barr virus, hepatitis C virus (HCV), Sjogren’s syndrome (18–21)] have been associated with multiple subtypes. In the last two decades, reports from individual epidemiological studies of NHL have suggested differences in risks among NHL subtypes for a wide range of risk factors, but most studies have lacked the statistical power to assess any differences quantitatively and have not systematically evaluated combinations of subtypes. One study assessed multiple risk factors and found support for both etiologic commonality and heterogeneity for NHL subtypes, with risk factor patterns suggesting that immune dysfunction is of greater etiologic importance for diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma than for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (22). However, that analysis was limited to approximately 1300 NHL cases and considered only the four most common NHL subtypes. Pooling data from multiple studies through the International Lymphoma Epidemiology Consortium (InterLymph) have provided substantial insight into associations between specific risk factors and NHL subtypes, with evidence that family history of hematologic malignancy, autoimmune diseases, atopic conditions, lifestyle factors (smoking, alcohol, anthropometric measures, and hair dye use), and sun exposure are associated with NHL risk (19,21,23–32). However, no previous study has compared patterns of risk for a range of exposures for both common and rarer NHL subtypes. We undertook the InterLymph NHL Subtypes Project, a pooled analysis of 20 case–control studies including 17 471 NHL cases and 23 096 controls, to advance understanding of NHL etiology by investigating NHL subtype-specific risks associated with medical history, family history of hematologic malignancy, lifestyle factors, and occupation. The detailed risk factor profiles for each of 11 NHL subtypes appear in this issue (15–17,33–40). In this report, we assess risk factor heterogeneity among the NHL subtypes and identify subtypes that have similar risk factor profiles.

Purpose The purpose of this study was to examine the long-term efficacy of an exercise regimen based on circular muscle strengthening (Paula method) as opposed to pelvic floor muscle training (PFMT) on stress urinary incontinence symptoms at 6 months postintervention. Subjects and setting Of 240 women who had initially participated in a randomized clinical trial, 143 women suffering from stress urinary incontinence participated in this follow-up study. Methods Subjects participated in a randomized controlled clinical trial comparing 2 exercise programs (12 private Paula lessons vs 6 group PFMT lessons) over a 12-week period. Of these, 143 women took part in the follow-up study: 64 from the Paula group and 79 from the PFMT group. Six-month follow-up data were gathered via telephone interviews. Results No significant deterioration in stress urinary incontinence symptoms occurred 6 months after completion of the interventions in either group. We found a statistically significant difference between the groups with regard to reported frequency of urinary leakage; 25 of subjects (39.7%) allocated to the Paula method reported a low frequency rate of incontinence episodes upon completion of the study as compared to 18 (22.8%) in the PFMT group (P = .03). Forty-nine of the 64 women in the Paula group (76.6%) and 62 of the 79 women in the PFMT group (78.5%) reported that they continued exercising 6 months after completion of the trial (P = .8). Conclusions Both intervention methods reduced frequency of urinary incontinence over a 6-month period. Long-term adherence was similar in both groups. Pelvic floor muscle training was associated with fewer sessions and decreased cost and fewer lessons needed as compared with the Paula method. Nevertheless, results also suggest that the Paula method achieves a lower frequency of urinary leakage than PFMT.

MoBa and the International Childhood Cancer Cohort Consortium (I4C) Terence Dwyer, Gabriella Tikellis, Akram Ghantous, Stanley Lemeshow, Siri E. Haberg, Jorn Olsen, Ora Paltiel, Jean Golding, Martha S. Linet, Zdenko Herceg, Monica C. Munthe-Kaas and Camilla Stoltenberg 1) The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Oxford, UK 2) The International Agency for Research on Cancer, Lyon, France 3) Murdoch Children’s Research Institute, Royal Children’s Hospital, University of Melbourne, Melbourne, Australia 4) The Ohio State University College of Public Health, Columbus, Ohio 5) Norwegian Institute of Public Health, Oslo, Norway 6) Department of Epidemiology, University of California, Los Angeles, CA, USA 7) School of Public Health and Department of Hematology, Hadassah-Hebrew University, Jerusalem, Israel 8) Centre for Child & Adolescent Health, School of Social & Community Medicine, University of Bristol, Bristol, UK 9) Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 10) Department of Pediatrics, Oslo University Hospital, Oslo, Norway

Although 90–95% of adults recover completely from Hepatitis B (HBV) infection, a minority are unable to clear the virus.[1][1] Epidemiological studies have demonstrated an increased risk of B-NHL among those with persistent HBV and B-NHL.[2][2]–[5][3] However, the roles of exposure per se

Fresh water scarcity has led to increased use of reclaimed wastewater as an alternative and reliable source for crop irrigation. Beyond microbiological safety, concerns have been raised regarding contamination of reclaimed wastewater by xenobiotics including pharmaceuticals. This study focuses on carbamazepine, an anticonvulsant drug which is ubiquitously detected in reclaimed wastewater, highly persistent in soil, and taken up by crops. In a randomized controlled trial we demonstrate that healthy individuals consuming reclaimed wastewater-irrigated produce excreted carbamazepine and its metabolites in their urine, while subjects consuming fresh water-irrigated produce excreted undetectable or significantly lower levels of carbamazepine. We also report that the carbamazepine metabolite pattern at this low exposure level differed from that observed at therapeutic doses. This "proof of concept" study demonstrates that human exposure to xenobiotics occurs through ingestion of reclaimed wastewater-irrigated produce, providing real world data which could guide risk assessments and policy designed to ensure the safe use of wastewater for crop irrigation.

In recent years, anti-CD20 antibodies have been increasingly used to treat lymphoproliferative and immune disorders. Chronic viral infections are infrequently reported in patients receiving these therapies. Enteroviral infection can cause life-threatening meningoencephalitis and other systemic chronic syndromes in immune deficient patients. We describe the clinical courses and outcomes of 6 patients from 2 tertiary care institutions who developed chronic enteroviral infection with neurological manifestations, after combined chemoimmunotherapy with rituximab for B-cell lymphoma. We review the literature that includes 10 sporadic reported cases of chronic enteroviral meningoencephalitis attributed to rituximab therapy. It is a rare disease, and its diagnosis is often elusive. We propose that low immunoglobulin G levels are the main risk factor for developing chronic enteroviral infection and emphasize the need for a high index of suspicion, early diagnosis, and intervention in this iatrogenic and potentially fatal complication.